A diagnostic test that carries out a multiple genetic analysis aimed at evaluating the susceptibility to the development of Colorectal cancer or Familial Adenomatous Polyposis

What is a tumour?

Cancer nowadays is considered a pathology with a genetic component that occurs when cellular growth is out of control. Our body cells receive signals telling them when to grow and multiply and when such growth must stop. In a tumour, such cells do not respond to control signals and grow and multiply abnormally, spreading to different parts of the body, due to changes in their DNA.
The event leading to the alteration of genetic functions is called “mutation”. When a gene is affected by mutation for different causes (biological, chemical and physical), information to the cell will not be adequate for its functions.

Is cancer hereditary?

Neoplasms are mostly pathologies caused by multiple factors generated by
genetic and environmental risk factors. Most tumours are “sporadic”, that is,
they arise in the general population without any clear signs of a genetic
susceptibility. In these types of tumours, DNA alterations (mutations) randomly
develop in somatic cells, namely, those cells creating every organ and system of
our body. These mutations develop in the DNA of a small group of cells and
generate the genetic error that is perpetrated in the descendants of those
cells. After having accumulated in an organ, they initially replace the healthy
cells of that organ and then spread to other organs, both nearby and distant
(metastasis). There are forms of tumour called "familial", when people
affected by cancer in the family are close relatives. Cancer familiarity is a
significant risk factor, especially when common environmental risk factors are
also shared (lifestyles, diet, polluting agents, etc.) without a specific
genetic alteration that makes the subject more susceptible to the disease.
Only a small, but significant, percentage of tumours are “hereditary”. Estimates
say that around 5-10% of breast cancers and 10-25% of ovarian cancers have a
hereditary component. In these tumours, DNA mutations occur in germ or
reproductive cell and, therefore, may be passed on to the person's offspring. At
birth, the child will show the genetic defect in one or more genes in all cells
of the body and, therefore, will be susceptible to the development of a neoplasm
when, during his/her life, other mutations occur.

When a new person is
conceived, s/he acquires two pairs of each gene, one pair from the father and
one from the mother. Any genetic mutations in the DNA of the parents are,
therefore, passed on to children. If one of the parents has a mutation in one of
the cancer-generating genes (hereditary tumour), the offspring has a 50% chance
of inheriting that mutation. People inheriting a germ cell mutation are born
with a copy of the mutated gene. These people do not inherit the tumour, but
only the susceptibility to develop that type of cancer more easily, compared to
the general population.

ColonScreen® Test

ColonScreen®
is a diagnostic test developed by GENOMA Group that carries out a multiple genetic analysis aimed at evaluating the susceptibility to the development of Colorectal cancer or Familial Adenomatous Polyposis. Therefore, the test identifies patients with the risk of developing the aforesaid neoplasms by analysing their DNA.

The genetic susceptibility test is addressed to people who from a thorough family history, show a high and concrete incidence of neoplasms in previous generations and, therefore, have a high risk of carrying a germinal mutation.

A hereditary form of cancer may be present when
the family has:• Several individuals
affected by the same type of cancer or
correlated cancers, • Individuals affected
by multiple tumours,• Tumours that arise at
a young age.

In particular:• Colorectal cancer diagnosed
≤ 50 years;• Endometrial or
ovarian cancer with a family history of
gastrointestinal cancer; • Subjects with
more than one cancer associated to the Lynch
syndrome (e.g. colorectal and endometrial
cancer); • Three or more cases of
colorectal, ovarian, endometrial, gastric cancer
or other types of cancer associated with the
Lynch syndrome in the family; • Results of
the Microsatellite or immunohistocemical
instability test in the cancer showing a lower
capacity of repairing DNA replication errors;
• Multiple primary tumours in the same
patient; • Several members of the family (on
the same side) with colorectal cancer or other
types of cancer. • A known mutation in the
family in one of the genes associated with
colorectal cancer/polyposis susceptibility.

The geneticist, with the informed consensus of
the person, will decide whether a DNA mutation
diagnostic test is necessary.

How does the ColonScreen® test work?

ColonScreen®
test is carried out with a blood sample. The DNA is
isolated from the nucleated cells through a
complex laboratory analysis and amplified via PCR.
Then, with a state-of-the art technological massive
parallel sequencing (MPS) process that uses
Next Generation Sequencing (NGS) techniques
with ILLUMINA sequencers, 12 genes
(exons and adjacent intrionic regions, ± 5 nucleotides)
are completely sequenced at high reading depth (Table 1).
The chosen genes are often involved in hereditary
susceptibility to the formation of Colorectal cancer or
Familial Adenomatous Polyposis.

The resulting genetic
sequences are analysed with an advanced
bioinformatics analysis, to find mutations of the
examined genes, if present.

Accuracy of the ColonScreen® test

Present DNA sequencing techniques produce results with more than 99% accuracy. Even though this test is very accurate, the limits of the examination need to be considered.

Test Limits

This examination analyses only genetic diseases and genes listed in Table 1
and cannot detect:

• Mutations positioned in the intrionic regions beyond ± 5 nucleotides from the breakpoints;
• Deletions, inversions, or duplications with a value of more than 20 bps;
• Germline mosaicism (i.e. mutations only in the gametes).

A “NEGATIVE” - No mutations result for the examined genes does not exclude the possibility that mutations are not present in a region of the genome that was not explored during the examination.
Some regions of our DNA may not be sequenced or have a lower coverage than the limitations set by GENOMA Group experts to guarantee an accurate examination of gene variations. These regions, therefore, are not included in the examination if they do not meet the requested qualitative standards.
In some cases the result of genome testing may reveal DNA variations or mutations with an unknown or unclassifiable clinical meaning within the current medical and scientific knowledge.
The interpretation of genetic variations is based upon the most updated knowledge available upon examination. Such interpretation may change in the future, when new scientific and medical information on the structure of the genome are acquired and may affect the evaluation of the genetic variations themselves.

What are the benefits of the ColonScreen® test?

The possibility to detect subjects at risk of developing
a neoplasm is the best way for an early diagnosis of
cancer and, therefore, to decrease mortality in that
type of disease. Members of families with high risks of
inheriting cancer and especially those that were
directly affected by a neoplasm, genetic counselling and
may discuss his/her clinical and genetic situation with
the geneticist. This assessment may lead to a genetic
test to evaluate whether the patient is a carrier of a
mutation that increases susceptibility to the
development of a specific tumour. If the test result is
positive, the analysis may be extended to the relatives
of the patient, in order to find those at risk.

The information from the genetic test may offer several benefits, such as:

Finding
family members with a high risk of developing
cancer;

The development of an adequate medical check
plan for high-risk subjects, in order to
promote early diagnosis of cancer;

Awareness that the genetic mutations may be
transferred to the offspring and the detection
of high-risk offspring with germinal genetic mutations;

The possibility to undergo prevention
therapies.

Results of the ColonScreen® test

“POSITIVE“Presence of one or more mutations:
the
result shows that there are one or more mutations in
one (or more) genes leading to hereditary
susceptibility to the development of colon cancer; the test, therefore, shows a mutated
copy of the gene. During a genetic consultancy
session, our geneticist thoroughly explains the test
results and calculates the likelihood of developing
the specific cancer associated to that mutation
detected in a specific gene.

A positive result does not necessarily mean that the patient with a mutation will develop a tumour; it only shows susceptibility to developing that type of tumour in the patient, or rather, the person has a higher risk level compared to a person without that specific mutation. In fact, not all people carrying mutations develop neoplasms. Although such mutations significantly increase the chance of developing a tumour, the cancer does not develop until the normal copy of the corresponding gene is mutated during the life of the person.
Since everyone inherits two pairs of the same gene, a mutation must occur in each pair to cancel the function of such gene. The acquisition of a new mutation may, therefore, directly lead to a tumour. Identifying cancer-susceptibility mutation allows us to develop an intense clinical check plan and evaluate preventive surgery. A mutation also leads to the examination of other relatives at risk if they want to check their situation. In relatives the test is a predictive analysis, because it detects, within these families, the carriers of the mutation and people that do not carry the mutation, finding exactly those people with a high chance of developing a tumour and those whose risk is at the same level as the general population. That way, carriers can start specific check protocols for early diagnosis or prevention, while the latter will be screened with the same protocols as the general population.

“NEGATIVE”No mutations: the results show no mutations in the examined genes. However, a negative result does not necessarily mean that the patient does not risk developing a tumour. These people have the same chance of developing cancer as the general population because most of these types of tumours are sporadic in nature.

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About us

GENOMA: a rich heritage combining technologies and
people, a model for quality, professional expertise and
competencies.

GENOMA is a highly specialised
diagnostic centre in Italy, renowned for its
contribution to the advancement of molecular
diagnostics. The laboratory is also renowned
internationally thanks to its collaboration with
scientific networks and prestigious research projects.

GENOMA, incorporated in 1997, is the point of
reference for high-tech examinations. It is mainly a
"service" centre for highly specialised prenatal and
postnatal genetic, cytogenetic and molecular
examinations.

GENOMA is considered as one of the most
advanced molecular diagnostics centre in Europe and its
head offices are in Rome and Milan. The laboratories are
in a modern, high-tech building and cover a surface of
more than 4,000 sqm. The centre uses state-of-the-art
instruments and technologies and works at high quality
levels.

GENOMA professionals have been working in
genetics for more than 20 years. A team of more than 100
professionals, including geneticists, molecular
biologists, gynaecologists, researches and laboratory
technicians work together operating in the field of
cytogenetic and molecular diagnostics for clinical
applications and research and are led by Dr. Francesco
Fiorentino inside a centre with very high technical and
scientific standards.

GENOMA works all over Italy
and abroad in Europe, the United States and the Middle
East, providing specialised diagnostic support for
public and private health clinics, examination
laboratories, health centres, hospitals, private
clinics, general outpatients' clinics, medically
assisted procreation centres and physicians specialising
in different fields. Our laboratories receive
biological samples from more than 5,000 health centres
and hospitals every day. The integrated approach of the
Centre is aimed at performing extremely high volumes of
examinations; more than 100,000 genetic tests,
constantly increasing, are carried out every year.

One of the features of the Group is a well-organised
network of services, one of the most comprehensive in
Italy and abroad, allowing the centre to offer its
patients and their physicians innovative diagnostic
solutions for any clinical need. With a list of more
than 1,500 genetic tests available directly in our
laboratories and divided into 20 areas of application,
GENOMA is able to meet increasingly specialised requests
in cytogenetic and molecular diagnostics, providing its
customers with a highly specialised, precise, effective
and rapid service.

GENOMA is a laboratory with one
of the longest, wide-ranging experience in Europe in
prenatal diagnostics. Thanks to this heritage, the Group
can offer expectant mothers and their physicians
state-of-the art technologies for foetal chromosome and
genetic diseases diagnostics.